Small steps lead to big discoveries

A common disease that affects both people and canines appears to have very different catalysts in each species, new research from the University of Minnesota (UMN) College of Veterinary Medicine (CVM) found. 

Many of the conditions physicians treat in people act similarly in dogs. Past UMN CVM research has found the same targets are responsible for fast-growing osteosarcoma in humans and dogs, expanding the use of drugs for both species. 

Science is anything but linear, though, and narrowing in on a solution that can prevent or treat a condition involves years of ruling out what is not the answer. Those stepping stones are critical pieces of research. While individual studies may not on their own yield groundbreaking discoveries, their collective contributions to a larger body of knowledge are what drives much of scientific progress.

Nicole Tate, postdoctoral research associate in the CVM Equine Genetics and Genomics Laboratory, and the CVM Canine Genetic Lab team wanted to see if humans and their dogs shared genetic risk factors of primary hypertriglyceridemia, a condition that causes too much fat in the blood.

Primary hypertriglyceridemia is common in older miniature schnauzers and the condition is linked to pancreatitis. The disease also affects more than 40 percent of adults over age 60. Genetic variants in just five genes are responsible for more than half the cases. In the rest of these cases, scientists believe genetic variations in multiple genes spur the condition. 

Taking what they know about the genes that carry these variants in humans, Tate and the Canine Genetics Lab team looked at candidate genes—which are genes previously known to be associated with a certain condition—in miniature schnauzers. 

The genetic sequences of six candidate genes revealed that dogs, unlike people, didn’t appear to carry variants in these genes that explain high levels of fat in the blood. 

“The absence of variants in these candidate genes contribute to the growing evidence that hypertriglyceridemia is likely a complex disease in miniature schnauzers,” Tate said. This complexity suggests that both environmental factors, such as diet and exercise, and multiple genetic factors in combination are what ultimately determine if the disease develops.

In a second study, Tate and the CVM Canine Genetics team looked at the amount of lipoproteins—the molecules that carry fats in the blood, each with distinct characteristics—in Miniature schnauzers who had hypertriglyceridemia. They found there are several different configurations of these molecules in these dogs. 

“Even dogs with similar triglyceride concentrations are likely to have differences in their lipoprotein profile,” Tate said. In total, they revealed six distinct lipoprotein patterns. “Hypertriglyceridemia is likely a spectrum in miniature schnauzers.”

Genetic sequencing as a science is young, and UMN houses unique resources to investigate banked genetic code from humans and their canine companions. The university is a leader in comparative medicine, which utilizes biological similarities in people and animals to study diseases that impact both. The work can yield treatments for all. But such progress requires careful, incremental advances, as Tate and the research team demonstrate through this body of work.

The CVM Canine Genetics Lab is continuing to explore what other genes could be contributing to hypertriglyceridemia in miniature schnauzers. Moving forward, Tate said investigating the relationship between the metabolome—metabolites in the body—or microbiome and hypertriglyceridemia could reveal deeper insights. 

Read the full studies in Genes and the Journal of Veterinary Internal Medicine.